Twelve hour metabolic rhythms have been performed on six maturity-onset diabetic subjects during successive periods of therapy with phenformin, metformin, and glibenclamide. Moderate control of blood glucose concentration was achieved with phenformin and metformin, the lowest concentrations being found with glibenclamide. Mean blood lactate concentration was grossly elevated during phenformin therapy, moderately elevated with metformin and normal during glibenclamide treatment. Similar patterns were found for the lactate/pyruvate ratio, alanine, glycerol and ketone bodies. Serum triglyceride concentrations were significantly higher during phenformin treatment than with the other two regimes. Serum insulin concentration was higher on glibenclamide than with either biguanide. Most of these effects of the biguanides could be accounted for by an inhibitory effect on hepatic gluconeogenesis. It is concluded that the use of biguanides as hypoglycaemic agents in diabetes is associated with the production of multiple metabolic abnormalities.

Twelve hour metabolic studies have been performed in two groups of maturity-onset diabetics treated either by sulphonylurea and metformin therapy or sulphonylurea therapy alone. There was no significant difference in blood glucose concentration between the two groups although serum insulin concentration was significantly higher in the group treated by sulphonylurea therapy alone. Concentrations of several intermediary metabolites were higher when metformin formed part of the therapy. Thus, mean blood lactate, pyruvate, alanine and total ketone body concentrations and the lactate/pyruvate ratio and 3-hydroxybutyrate/acetoacetate ratio were all significantly elevated during sulphonylurea and metformin therapy. It is concluded that the use of metformin with a sulphonylurea results in widespread abnormalities in blood concentrations of intermediary metabolites.

Dapsone is widely used in dermatological practice. The case of a Greek female patient is reported who had a severe, acute, haemolytic episode shortly after commencing dapsone therapy, despite a normal glucose-6-phosphate dehydrogenase (G6PD) screening test. A subsequent quantitative assay revealed reduced levels of G6PD consistent with the heterozygous state. This illustrates that routine screening tests may fail to detect the decreased levels of (G6PD) which occur in female heterozygotes. Since these patients are at risk of severe dapsone-induced haemolysis, the need for quantitative G6PD assays in females from susceptible racial groups is emphasized.

Twelve hour metabolic rhythms have been determined in two groups of subjects during combined therapy with a sulphonylurea and phenformin 50 mg twice daily. Subjects with clinical evidence of complications of diabetes showed greater abnormalities in concentrations of blood intermediary metabolites than a group of subjects without complications despite similar mean blood glucose concentrations in the two groups (7.6 mmol/1 with complications; 7.3 mmol/1 without complications). Mean blood lactate (1.93 mmol/1 v 1.39 mmol/l), alanine (0.56 mmol/1 v 0.43 mmol/1), total blood ketone bodies (0.20mmol/l v 0.14mmol/1) and several other intermediary metabolites and their ratios were significantly higher in the group with diabetic complications. It is suggested that the differences between the two groups may arise from impaired disposal of phenformin leading to higher blood concentrations in the group with diabetic complications, despite normal liver function tests and plasma creatinine concentration. It is probable that this accumulation of phenformin results in more pronounced effect upon blood glucose and other intermediary metabolites. Thus, the metabolic abnormalities previously reported in patients treated by phenformin alone are also present during combined sulphonylurea and phenformin therapy, and in the presence of diabetic microangiopathy these abnormalities are accentuated.

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